The major objective of this project is to determine whether pancreas transplantation changes the course of diabetic neuropathy. The hypothesis to be tested is that establishment of a constant euglycemic state by a functioning pancreatic graft will halt or prevent progression of the neuropathy. To accomplish this the study will follow the course of the polyneuropathy in type I diabetic patients treated by either pancreas transplantation or tight insulin therapy for 5 years. The spectrum of nerve involvement in each patient will be evaluated, at onset of the study and at selected intervals, by clinical history and examination and by performing quantitative tests of function in several types of large and small diameter motor and sensory nerve fibers of the somatic and autonomic nervous systems. These will include nerve conduction, thermal and mechanical sensation, cardiorespiratory reflexes, sweating activity, and alternate motion rate. Efforts will also be continued to improve existing tests and to devise new, more sensitive methods to quantify neural function. Our long term objectives are: 1) to compare the effects of treatment by pancreas transplantation and strict insulin control on the overall course of the neuropathy, 2) to determine whether the effects differ for the various types of nerve fibers, 3) to differentiate the neuropathic effects of uremia from those of the diabetes itself, and 4) to accomplish these objectives using a combination of established methods and tests that we design to determine function in a variety of nerve fibers.